This research concerns various apparently related observations on the effects of vaccinia virus and of 3-methylcholanthrene (MCA) on the skin of mice: (1) Whether the development of leukemia in MCA-painted BALB/c X AKR Fl hybrids grafted with AKR skin might involve a latent leukemogenic virus present in the grafted skin. (2) Whether MCA painting induces skin changes that influence the acute effects of vaccinia in MCA-painted skin. (3) Whether latent leukemogenic viruses play a role in the skin resistance to vaccinia infection of mice which are highly susceptible to either spontaneous of MCA-induced leukemia. (4) To further elucidate results relating to the inheritance of high susceptibility to the induction by MCA painting of either skin tumors or leukemia, and regarding also the inheritance of either spontaneous or MCA-induced leukemia. (5) Whether the acute effects of vaccinia on the skin of mice will modify the role of the virus in eliminating MCA- induced papillomas and delaying the development of malignant tumors.